The invention relates to novel extracts obtained by extraction of ripe complete soya beans or from oil-free soya flour (Glycine max (L.) MERRIL, Leguminosae family), their production and formulations containing these extracts. The novel extracts are characterized by their content of isoflavones and saponins in defined ratios.
It is known that soya contains saponin and isoflavone components in addition to saccharide and amino acid components, as well as proteins and mineral salts in amounts which depend on their geographical origin and the conditions under which the plant was cultivated and harvested.
The saponin contents have been divided into three classes depending on the chemical structure of their triterpene components: soya saponins of groups A, B and E (Okubo K. et al., ACS Symp., Ser. 546, 330, 1994).
 R1R2R3Group ASaccharideSaccharideOHchainchainGroup BSaccharideOHHchainGroup ESaccharide—OHchain
Isoflavone components consist of glucoside isoflavones (daidzin, genistin and glycitin) which can contain acyl radicals, e.g. malonyl radicals, linked to the saccharide chain.
 R1R2R3DaidzinHHD-GlucoseGlycitinOCH3HD-GlucoseGenistinHOHD-GlucoseDaizdeinHHHGlyciteinOCH3HHGenisteinHOHH
According to biomedical literature and epidemiological information published in recent years, principally in relation to populations of the East, which consume soya-based foods to a great extent, the use of these foods to a high degree reduces pre-menopausal and post-menopausal symptoms in women (A. Cassidy, Proceedings of the Nutrition Society, 1996, 55, 339–417) These facts, which still lack a clear scientific basis, are usually ascribed to the isoflavone aglycones genistein, daidzein and glycitein, which are present in the various soya-based foods.
Isoflavones are usually considered to be plant oestrogens, and numerous in-vitro studies have shown that these substances act in a mechanism competing with mammalian oestrogens with an activity which is rated lower by a factor of 500 to 1000 than that of oestradiol (D. A. Shutt and R. I. Cox, Journal of Endocrinology, 1972, 52, 299–310).
According to further biomedical literature and epidemiological information published in recent years, principally relating to population groups in the East, which consume soya-based foods to a great extent, the use of these foods decreases to a high degree breast cancer in women and cancer of the prostate in men (A. Nomura, B. E., Henderson J. Lee, American Journal of Clinical Nutrition, 1978, 31, 2020–2025; T. Hirayama in Diet, Nutrition and Cancer, 1986 pp. 41–53, Y. Hayashi, M. Nagao, T. Sugimura, S. Takayama, L. Tomatis, L. W. Wattenberg and G. N. Wogan eds. Tokyo: Japanese Scientific Society Press; R. K. Severson, A. M. Y. Nomura, J. S. Grove, G. N. Stemmerman, Cancer Research, 1989, 49, 1857–1860). Also, these facts, which still lack a clear scientific basis, are usually ascribed to the isoflavone aglycones genistein, daidzein and glycitein which are present in the various soya-based foods.
These isoflavones have been studied in in-vitro models with regard to their capacity to interact with protein kinases, in particular with tyrosine kinase, enzymes which appear to play a role in proliferation of tumour cells.
Numerous attempts have been made recently to prepare drugs based on soya extracts for the preventive treatment of pre-menopausal and post-menopausal symptoms and also for the preventive treatment of cancer. Some patents or patent applications describe compositions of novel soya extracts obtained by chemical or enzymatic hydrolysis of the glucoside isoflavones present in soya beans or soya bean sprouts (Kikkoman Corp. J-08291191; Kikkoman Corp. J-07173148; Kelly GE WO-9323069; Kikkoman Corp. J-0511707566). All of these publications are concerned solely with the preparation of isoflavones of high concentration and activities with regard to the control of pre-menopausal and post-menopausal disorders and to antitumour activity.
It has now been found, that in contrast to that described previously, extracts which contain glucoside isoflavones and group B soya saponins in defined ratios are considerably more active than isoflavones alone as regards both, the prevention or treatment of pre-menopausal and post-menopausal symptoms and the prevention or treatment of cancer.
A further aspect related to the extract of the invention is concerned with alcohol abuse and alcohol dependency or alcohol addicition. These are phenomena which can be summarized under the term “alcoholism” and form a serious problem of the entire modern society (Gessa G. L., “Bisogno compulsive di bere e principio del piacere” [The compulsion to drink and the pleasure principle] in Medicina delle tossicodipendenze [Medicine of drug dependency] II, 5 (1994)). In Italy, for example, more than 9% of the population (about 5 million) are heavy drinkers and more than 1 million are alcohol-dependent (Calamo-Spechhia F. P., “Epidemiologia dell'alcolismo in Italia” [Epidemiology of alcoholism in Italy] in Atti del VII Congresso Nazionale della S.I.A. [Reports of the 7th National Congress of the S.I.A.] Mediserve, Rome, 295–301 (1991)). These numbers are increased when countries such as the USA are taken into account, where more than 13 million are alcohol-dependent. Alcohol abuse and actual alcohol dependency lead to very high public expenditure (since 1991, in the USA about 200 billion dollars per year have been consumed) and are causes of great social and psychological damage to those affected.
Existing attempts to treat alcoholism in addition to those of a psychological nature (group therapy etc.) consist of applying drugs such as disulfiram and calcium carbamide, which act on alcohol metabolism, hepatic aldehyde dehydrogenase being inhibited and therefore the emetic acetaldehyde level being increased, together with all the unwanted phenomena which occur in the course of alcohol intake.
According to the prior art, the only plants whose derivatives were used for treating alcoholism are Pueraria lobata (Radix puerarie) and Salvia miltiorrhiza, which are very widely used in traditional Chinese medicine and form the subject-matter of the Patent Applications WO 93/00896 and WO 96/35441. In addition to the use of the extracts, these patent applications claim the use of pure substances such as daidzein and its semisynthetic derivatives in WO 93/00896, or diterpenoids, such as tanshinone and miltirone in WO 96/35441. An effect on alcohol dehydrogenase with the occurrence of the above-described side effect has been disclosed for the isoflavone derivatives, while the same mechanism has been excluded for the diterpenoid compounds. Furthermore, Patent Application WO 96/36332 disclosed the effect of forskolin in the reduction of alcohol consumption.
In addition to the above mentioned prior art WO 96/10341 discloses food or health products comprising substantially pure hypocotyls of soya seeds. No reference is made to the extraction procedure and to the ratio between isoflavones and saponins according to the present invention.
U.S. Pat. No. 4,428,876 discloses a process for isolating saponins and flavonoids from leguminous plants. The there disclosed extraction of soybean with 0.4% aqueous sodium hydroxide makes the final extract different from that of the present invention. Again, no reference is made to the ratio between isoflavones and saponins according to the present invention.
JP 59088064 is directed to the isolation and the use of saponins only. The same applies to DE 34 00 258. Similarly JP 61036225 is directed to the isolation and purification of saponins and JP 62005917 to the preparation of pure saponins completely free of isoflavones. JP 4036242 concerns the preparation of pure saponin or of an extract having a high saponin/isoflavone ratio as an antiinflammatory compound.
EP-A-426 998 discloses the preparation of isoflavones from soybean and in particular of genistine and daidzine malonate. No reference is made to the extraction of saponins and to the ratio between isoflavones and saponins.
JP 63245648 is directed to the preparation of soybean food material devoid of saponins and isoflavones which are considered harshness components rendering the food unedible.
Mark Messina et al., Journal of the National Cancer Institute, Vol. 83, No. 8, Apr. 17, 1991, pages 541–546 is directed to the role of soy products in reducing risk of cancer already reported in scientific literature. Neither this document nor other literature, however, refer to an extract containing saponins and isoflavones in the ratio of this invention, let alone the pharmacological effect obtainable by such a specific extract.